Obesity and its associated diseases, including type 2 diabetes, coronary heart disease and certain forms of cancers, are major public health challenges for the 21st century. The World Health Organisation (WHO) has declared that global childhood and adult obesity levels have reached epidemic proportions with the incidence in both developed and developing countries increasing at an alarming rate (WHO, Obesity: Preventing and managing the global epidemic, Report on a WHO Consultation, 2000). It is predicted that up to 58% of the world's adult population will be overweight or obese by 2030 (Kelly, T., et al., Int. J. Obes. 32:1431-7, 2008).
Diabetes is a chronic disease which occurs when the pancreas does not produce enough insulin (type 1 diabetes) or when the body cannot effectively use the insulin it produces (type 2 diabetes). Type 2 diabetes, which is related to being overweight, obesity and physical inactivity, accounts for around 90% of all cases of diabetes, and the number of cases is increasing globally. WHO predict that diabetes deaths will double between 2005 and 2030 (WHO Fact Sheet No. 312, 2011), so that by 2030 diabetes will become the seventh leading cause of death world-wide.
Disease risk related to obesity, such as type 2 diabetes disease risk or cardiovascular disease risk, increases independently with increased body mass index (BMI). This risk has been quantified as a five percent increase in the risk of cardiac disease for females, and a seven percent increase in the risk of cardiac disease for males, for each point of a BMI greater than 24.9 (see Kenchaiah, M. D., et al., N. Engl. J Med. 347:305, 2002; Massie, B. M., N. Engl. J Med. 347:358, 2002). In addition, there is substantial evidence that weight loss in obese persons reduces important disease risk factors. Even a small weight loss, such as 10% of the initial body weight, in both overweight and obese adults has been associated with a decrease in risk factors such as hypertension, hyperlipidemia, and hyperglycemia. Recently it has been shown that considerable weight loss can effectively cure type 2 diabetes (Lim, E. L., et al, Diabetologia 54:2506-14, 2011).
The cause of obesity is complex and multi-factorial. Increasing evidence suggests that obesity is not a simple problem of self-control but is a complex disorder involving appetite regulation and energy metabolism. Although the etiology of obesity is not definitively established, genetic, metabolic, biochemical, cultural and psychosocial factors are believed to contribute.
Diet and exercise provide a simple process to decrease weight gain, however overweight and obese individuals often cannot sufficiently control those factors to effectively lose weight. Pharmacotherapy is available; several weight loss drugs have been approved by the Food and Drug Administration that can be used as part of a comprehensive weight loss program. However, many of these drugs have proved to have serious adverse side effects and have had to be withdrawn. An acceptable pharmacotherapy must be acceptable for use over an extended period of time, and so risks of side-effects must be low. When less invasive methods have failed, and the patient is at high risk for obesity related morbidity or mortality, weight loss surgery is an option in carefully selected patients with clinically severe obesity. However, these treatments are high-risk, and suitable for use in only a limited number of patients.
It is not only obese subjects who may wish to lose weight. People with weight in, for example, the upper part of the recommended range, may wish to reduce their weight to bring it closer to the ideal weight, or those with a healthy weight may wish to have assistance in maintaining that weight by preventing gaining weight. Thus, a need remains for agents that can be used to effect weight loss in overweight and obese subjects as well as subjects who are of normal weight.
The Foresight report highlighted appetite regulation as a major target in the dietary treatment of obesity (Butland, B. J., et al., Foresight Tackling Obesities: Future Choices—Project Report, Government Office for Science, 2007). Of particular interest is the concept of functional foods or novel products which increase satiety. The goal is to design foods or dietary regimens that increase the sense of fullness and encourage the individual to stop eating sooner, thus reducing total energy intake (Hill, J. O., Peters, J. C., Br. J. Nutr. 88(suppl. 2):S213-8, 2002).
One goal of a successful pharmacotherapy or dietary treatment of obesity would be that it could be applicable at a public health level. This means a cost-effective treatment that can be safely applied at the population level to improve appetite regulation and prevent weight gain throughout life. An attractive strategy is the enrichment of foods with components that reduce appetite, food intake and/or calorie intake. A composition which could be added to staple food stuffs, such as bread, with no noticeable effect on palatability, would be easily accessible to the wider population and so applicable at a public health level.
There currently remains a need for further pharmacotherapy and dietary treatments of obesity which successfully regulate appetite, food intake and/or calorie intake, as well as such treatments which do not have unpleasant side effects. There also remains a need for pharmacotherapy and dietary treatments that can prevent weight gain in healthy or overweight subjects. The aim of the current inventors is to identify a treatment that reduces appetite, food intake and/or calorie intake and/or that can improve insulin sensitivity in a subject, and which may be applicable at a public health level.